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Spontaneous Proliferation of CD4(+) T Cells in RAG-Deficient Hosts Promotes Antigen-Independent but IL-2-Dependent Strong Proliferative Response of Naive CD8(+) T Cells


The fast and intense proliferative responses have been well documented for naive T cells adoptively transferred into chronic lymphopenic hosts. This response known as spontaneous proliferation (SP), unlike antigen-independent lymphopenia-induced proliferation (LIP), is driven in a manner dependent on antigens derived from commensal microbiota. However, the precise nature of the SP response and its impact on homeostasis and function for T cells rapidly responding under this lymphopenic condition are still unclear. Here we demonstrate that, when naive T cells were adoptively transferred into specific pathogen-free (SPF) but not germ-free (GF) RAG(-/-) hosts, the SP response of these cells substantially affects the intensity and tempo of the responding T cells undergoing LIP. Therefore, the resulting response of these cells in SPF RAG(-/-) hosts was faster and stronger than the typical LIP response observed in irradiated B6 hosts. Although the intensity and tempo of such augmented LIP in SPF RAG(-/-) hosts were analogous to those of antigen-dependent SP, the former was independent of antigenic stimulation but most importantly, dependent on IL-2. Similar observations were also apparent in other acute lymphopenic settings where antigen-dependent T cell activation can strongly occur and induce sufficient levels of IL-2 production. Consequently, the resulting T cells undergoing IL-2-driven strong proliferative responses showed the ability to differentiate into functional effector and memory cells that can control infectious pathogens. These findings therefore reveal previously unappreciated role of IL-2 in driving the intense form of T cell proliferative responses in chronic lymphopenic hosts.

Type Journal
ISBN 1664-3224 (Electronic) 1664-3224 (Linking)
Authors Kim, J.; Lee, J. Y.; Cho, K.; Hong, S. W.; Kim, K. S.; Sprent, J.; Im, S. H.; Surh, C. D.; Cho, J. H.
Responsible Garvan Author Prof Jonathan Sprent
Publisher Name Frontiers in Immunology
Published Date 2018-08-23
Published Volume 9
Published Pages 1907
Status Always Electronic
DOI 10.3389/fimmu.2018.01907
URL link to publisher's version